Cardiomyopathy in children is a serious disease which can result in death, disability, heart transplantation or serious heart rhythm disorders. Doctors know little about the causes of cardiomyopathy but would like to learn more. In fact, up to 50-75% of cases in children have no known cause. For this reason, the purpose of this study is to identify genes that cause cardiomyopathy or that influence how people with cardiomyopathy do over time. These findings could improve disease prevention, surveillance, early management, and prognosis.

Diagnosis of primary or idiopathic dilated, hypertrophic or restrictive cardiomyopathy. Diagnosis must have been made before the age of 18 and must be confirmed by established echocardiographic criteria or cardiac MRI (cMRI) at the time of diagnosis.

Detailed Description:

Pediatric cardiomyopathy is a heterogeneous genetic disease with high morbidity and mortality in which children often present with fulminant disease leading to death or transplant. The long-term goal of this project is to identify the genetic basis of cardiomyopathy and to correlate these findings with clinical phenotypes for risk stratification. These findings could improve disease prevention, surveillance, early management, and prognosis.

The specific aims of this study are:

To identify the disease-causing and disease-associated genetic variants underlying pediatric cardiomyopathy in a carefully phenotyped cohort.

To identify genotype-phenotype correlations that allow for risk stratification and improve management and therapy.

Exome sequencing will be used as part of a tiered genetic analysis in a large cohort of up to 700 pediatric cardiomyopathy subjects with systolic (dilated cardiomyopathy) or diastolic (hypertrophic or restrictive cardiomyopathy) dysfunction. The biological parent(s) of enrolled participants will also be approached about participating and providing a blood sample for genetic testing. In addition to the parent(s), the participants siblings and other relatives may also be approached regarding enrollment, based on the pedigree and family history.

This study will significantly increase our understanding of pediatric cardiomyopathy by defining the prevalence of mutations in genes known to cause cardiomyopathy as well as identifying novel disease-causing genes in the pediatric population. Genetic association tests will identify variants that modify disease. Novel bioinformatics and systems biology applications for interpretation of exome level genetic information will contribute fundamental knowledge and technical innovation to the translation of genomic data to clinical utility. These aims will provide critical genetic architecture data, identify variants with large effects, and enable genotype-phenotype correlations necessary for advancing management and therapy.

The Study will have two components: 1) clinical data collection by chart review and family interview, and 2) biospecimen collection and genetic testing.

Eligibility

Ages Eligible for Study:

Child, Adult, Senior

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Sampling Method:

Non-Probability Sample

Study Population

Pediatric cases of dilated, hypertrophic or restrictive cardiomyopathy and select relatives will be enrolled at 11 pediatric cardiology centers in the US and Canada.

Criteria

Inclusion Criteria:

Patient is alive. (except samples from deceased relatives who have consented for testing).Patients who are status-post heart transplant are eligible if pre-transplant longitudinal data are available.

Under age 18 years at the time of diagnosis of either primary or idiopathic dilated, hypertropic, or restrictive cardiomyopathy.

A diagnosis of cardiomyopathy which, at the time of diagnosis, was confirmed by echocardiographic criteria or cardiac MRI

Exclusion Criteria:

A patient is not eligible for enrollment if one or more of the following conditions are met at the time of presentation with cardiomyopathy:

Abnormal ventricular size or function that can be attributed to intense physical training or chronic anemia

Chronic arrhythmia, unless there are studies documenting inclusion criteria prior to the onset of arrhythmia (except a patient with chronic arrhythmia, subsequently ablated, whose cardiomyopathy persists after two months is not to be excluded).

Genetic syndrome or chromosomal abnormality known to be associated with cardiomyopathy

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01873963

Steve Lipshultz, Schotanus Family Endowed Chair of Pediatrics, Professor and Chair, Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine; President, University Pediatricians and Pediatrician-in-Chief, Children's Hospital of Michigan, Wayne State University